Effect of spironolactone on bilirubin metabolism in rat liver and small intestinal mucosa.
In vitro and in vivo experimental models were designed for the study of the effect of spironolactone (SP) on bilirubin metabolism in rat liver and small intestinal mucosa. In vitro studies included uptake of bilirubin by liver slices and intestinal sheets, determination of glucuronyltransferase activity in mucosal homogenates, and the handling of bilirubin by the isolated perfused liver after bilirubin overload. In vitro studies were carried out to measure the plasma disappearance rate of bilirubin and to determine the extent of bilirubin conjugation and biliary excretion of the pigment infused intravenously. The results obtained suggested that the mechanisms involved in the uptake of bilirubin by tissues were not influenced by SP pretreatment. Glucuronyltransferase activity in the small intestinal mucosa was significantly induced by SP, as previously observed in rat liver. Isolated perfused livers from SP-treated rats, as well as treated living rats, exhibited a greater than normal capacity for bilirubin excretion into bile at the expense of bilirubin diglucuronide. Conjugated bilirubin in the small intestinal mucosa of rats infused with unconjugated pigment was also increased after SP pretreatment. The results favoured the conclusion that SP is an inducer of bilirubin conjugation in the livers as well as in extrahepatic tissues, such as the small intestinal mucosa.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology*
D013148:Spironolactone; D014453:Glucuronosyltransferase; D001663:Bilirubin